Application of phytochemicals as drug molecules is an emerging field of research. In recent years there is growing interest in the use of phytochemicals as chemopreventive and chemotherapeutic agents.
Curcumin is a crystalline compound which has been traditionally used in medicine and cuisine in India. Curcumin (diferuloylmethane) is the major active component of turmeric. It has a low intrinsic toxicity, but a wide range of pharamacological activities including antioxidant, anti-inflammatory, antimicrobial, antiamyloid, and antitumor properties. Extensive research over the last 50 years has indicated that this polyphenol can both prevent and treat cancer. The ability of curcumin to induce apoptosis in cancer cells without cytotoxic effects on healthy cells makes it a potential compound for drug development against cancer. Molecular mechanisms that underlie curcumin's selective toxicity against tumor cells are not clearly understood.
Due to its various medicinal, biological and pharmacological activities, curcumin is high on demand and has high market potential. Its beneficial effects on various disease conditions has been already studied and described worldwide. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day orally.
All of these studies suggest that curcumin has enormous market potential in the prevention and therapy of cancer.
Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Curcumin has been administered to the animals via a variety of routes including topical, systemic, intravenous and oral routes of administration but with poor outcome.
In spite of its promising therapeutic index, the problem of its clinical use is not efficient because the biological activity of curcumin is severely limited due to its poor bio-availability. The reasons for reduced bioavailability within the body could be due to low intrinsic activity, poor absorption, high rate of metabolism, inactivity of metabolic products and/or rapid elimination and clearance from the body.
One of the major observations related to curcumin studies involve the observation of extremely low serum levels. A very recent study by Yang et al. showed that 10 mg/kg of curcumin given intravenously in rats gave a maximum serum curcumin level of 0.36 (0.05 μg/ml), whereas a 50-fold higher curcumin dose administered orally gave only 0.06 (0.01 μg/ml) maximum serum level in rats. An oral curcumin dose of 1 g/kg in rats produced a maximum serum curcumin level of 0.5 μg/ml after 45 min of curcumin dosing. Similarly, in a human clinical trial, 3.6 g of curcumin via oral route was found to produce a plasma curcumin level of 11.1 nmol/l after an hour of dosing.
Some of the possible ways to overcome these problems are being explored recently. Adjuvants, which can block metabolic pathways of curcumin, are one of the major means that are being used to improve its bioavailability. Nanoparticles, liposomes, micelles, and phospholipid complexes are other promising novel formulations, which appear to provide longer circulation, better permeability, and resistance to metabolic processes.
Nanoparticle based drug delivery approaches have been a recent research interest for rendering hydrophobic curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. Nanoparticle based systems for curcumin delivery is still in its infancy and much progress is warranted in this area. Liposomes are excellent drug delivery systems since they can carry both hydrophilic and hydrophobic molecules. It was found that liposomal vehicle is capable of loading more curcumin into cells than either HSA or aqueous-DMSO, and lymphoma cells showed preferential uptake of curcumin to lymphocytes. Micelles and phospholipids complexes can improve the gastrointestinal absorption of natural drugs, thereby giving higher plasma levels and lower kinetic elimination resulting in improved bioavailability.
Both in vitro and in vivo evaluations of a series of indium and gallium complexes of curcumin derivatives and curcumin have shown that the structural modification and/or complex formation of curcumin with metal ions may yield gallium and indium curcuminoids with potential therapeutic applications. Although many curcumin analogues are found to show improved biological activity over curcumin, specific evaluations of structural analogues and derivatives of curcumin to show improved tissue and plasma distribution are lacking.
Fibrin-antibiotic mixtures were used for assessing the possibility of using a biological carrier for local drug delivery and it was concluded that the antibiotic delivery was seen up to 4 days resulting in a prolonged release of drug. Pluronic tri-block copolymer micelle for the formulation of curcumin has been reported. In vitro release profile demonstrated slower and sustained release of curcumin from Pluronic micelles. The lyophilized form of the formulations exhibited good stability for long-term storage. A polymeric nano formulation of curcumin was reported to increase solubility and bioavailability in carbon tetrachloride induced liver injury in mice.
The University of South Floridas “oral curcumin in patients with hereditary allergy treatment research” has been completed and the compound was found to inhibit nuclear factor-B and the role of starting protein-1, thus inhibiting proteins that cause inflammation and anti-inflammatory substances produced. The research will affect the future of curcumin and promote the application on the market. Japanese companies promote the selling point on the edge of water-soluble curcumin, the compound makes the future of cosmetics and functional products in the field of application has been extended, using a fine-grained and unique technology that dramatically improves the absorption of curcumin. The, American company, Unibar demonstrated its Cur Qnetic curcumin formulation ingredients, the main component of 80% curcumin, vanillin and ginger compound formed, and claimed that the product supplements increase immunity and anti-inflammatory effect and the in vitro and in vivo studies confirmed this.
Therefore, the need exists in the art for an efficient drug delivery system for curcumin which will improve its bioavailability and sustained release.